Abstract
Squamous cell carcinoma is the most common malignant oral tumor in cats. The late presentation is one of the factors contributing to the detrimental prognosis of this disease. The immunohistochemical expression of the p53 tumor suppressor protein has been reported in 24% to 65% of feline oral squamous cell carcinomas, but no study has systematically evaluated in this tumor the presence of p53 encoding gene (TP53) mutations. The aim of this retrospective study was to determine whether p53 immunohistochemistry accurately reflects the mutational status of the TP53 gene in feline oral squamous cell carcinoma. Additionally, the prevalence of p53 dysregulation in feline oral squamous cell carcinoma was compared with that of feline non-neoplastic oral mucosa, in order to investigate the relevance of these dysregulations in cancer development. The association between p53 dysregulations and exposure to environmental tobacco smoke and tumor characteristics was further assessed.Twenty-six incisional biopsies of oral squamous cell carcinomas and 10 cases each of lingual eosinophilic granuloma, chronic gingivostomatitis and normal oral mucosa were included in the study. Eighteen squamous cell carcinomas (69%) expressed p53 and 18 had mutations in exons 5–8 of TP53. The agreement between immunohistochemistry and mutation analysis was 77%. None of non-neoplastic oral mucosa samples had a positive immunohistochemical staining, while one case each of eosinophilic granuloma and chronic gingivostomatitis harbored TP53 mutations. Unlike previously hypothesized, p53 dysregulations were not associated with exposure to environmental tobacco smoke. These results suggest an important role of p53 in feline oral tumorigenesis. Additionally, the immunohistochemical detection of p53 expression appears to reflect the presence of TP53 mutations in the majority of cases. It remains to be determined if the screening for p53 dysregulations, alone or in association with other markers, can eventually contribute to the early detection of this devastating disease.
Highlights
Squamous cell carcinoma is the most common malignant tumor of the oral cavity in cats, accounting for 60–70% of all oral malignancies. [1,2,3] Feline oral squamous cell carcinoma (FOSCC) most frequently involves the lingual region and dentate jaws, and may appear either as a necrotic ulcerative lesion or as a firm nodular swelling, generally associated with high local invasiveness and early bone lysis. [2, 3] regional and distant metastases have been reported, death most frequently occurs from complications associated with the primary tumor before metastatic disease has an opportunity to become clinically relevant. [3, 4,5,6] Due to location and rapid tumor progression, diagnosis is often late, and this largely limits the efficacy of treatments, including surgery, radiation therapy and chemotherapy
[21] an anecdotal report exists of a the presence of p53 encoding gene (TP53) mutation in a FOSCC, [23] no study has systematically evaluated the presence of TP53 mutations in these tumors, nor their association with IHC protein expression
The prevalence of p53 expression and mutations in FOSCC was compared with feline normal oral mucosa and oral inflammatory lesions, in order to investigate the relevance of p53 dysregulation in cancer development
Summary
Squamous cell carcinoma is the most common malignant tumor of the oral cavity in cats, accounting for 60–70% of all oral malignancies. [1,2,3] Feline oral squamous cell carcinoma (FOSCC) most frequently involves the lingual region and dentate jaws, and may appear either as a necrotic ulcerative lesion or as a firm nodular swelling, generally associated with high local invasiveness and early bone lysis. [2, 3] regional and distant metastases have been reported, death most frequently occurs from complications associated with the primary tumor before metastatic disease has an opportunity to become clinically relevant. [3, 4,5,6] Due to location and rapid tumor progression, diagnosis is often late, and this largely limits the efficacy of treatments, including surgery, radiation therapy and chemotherapy. Somatic mutations in the TP53 gene are the most frequent alterations in human head and neck squamous cell carcinoma (HNSCC), detected in up to 85% of cases, and have been related to tobacco carcinogenesis. [21] an anecdotal report exists of a TP53 mutation in a FOSCC, [23] no study has systematically evaluated the presence of TP53 mutations in these tumors, nor their association with IHC protein expression. The aim of this study was to determine whether p53 IHC accurately reflects the mutational status of the TP53 gene in FOSCC, and to investigate the relationship between p53 dysregulations and ETS exposure in cats. The prevalence of p53 expression and mutations in FOSCC was compared with feline normal oral mucosa and oral inflammatory lesions, in order to investigate the relevance of p53 dysregulation in cancer development
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